2.02012-05-31 13:46:47 -06002015-09-13 12:56:10 -0600ECMDB01173M2MDB0002825'-Methylthioadenosine5-Methylthioadenosine is a normal metabolite in Cysteine and methionine metabolism. Spermidine synthase (putrescine aminopropyltransferase)(EC:2.5.1.16) catalyzes the its formation and it is then converted to 5-Methylthio-D-ribose via S-adenosylhomocysteine/5'-methylthioadenosine nucleosidase [EC:3.2.2.9]. (KEGG)1-(6-amino-9H-Purin-9-yl)-1-deoxy-5-S-methyl-5-thio-b-D-ribofuranose1-(6-amino-9H-Purin-9-yl)-1-deoxy-5-S-methyl-5-thio-b-delta-ribofuranose1-(6-amino-9H-Purin-9-yl)-1-deoxy-5-S-methyl-5-thio-b-δ-ribofuranose1-(6-Amino-9H-purin-9-yl)-1-deoxy-5-S-methyl-5-thio-beta-D-Ribofuranose1-(6-Amino-9H-purin-9-yl)-1-deoxy-5-S-methyl-5-thio-beta-delta-Ribofuranose1-(6-amino-9H-Purin-9-yl)-1-deoxy-5-S-methyl-5-thio-β-D-ribofuranose1-(6-amino-9H-Purin-9-yl)-1-deoxy-5-S-methyl-5-thio-β-δ-ribofuranose5'-(Methylthio)-5'-deoxyadenosine5'-(Methylthio)adenosine5'-<i>S</i>-methyl-5'-thioadenosine5'-Deoxy-5'-(methylthio)adenosine5'-Methylthioadenosine5'-S-Methyl-5'-thio-Adenosine5'-S-Methyl-5'-thioadenosine5-Methylthioadenosine<i>S</i>-methyl-adenosineMethylthioadenosineMTAS-Methyl-5'-thioadenosineS-Methyl-5-thioadenosineS-Methyl-adenosineThiomethyladenosineC11H15N5O3S297.334297.089560061(2R,3R,4S,5S)-2-(6-amino-9H-purin-9-yl)-5-[(methylsulfanyl)methyl]oxolane-3,4-diolmethylthioadenosine2457-80-9CSC[C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C=NC2=C1N=CN=C2NInChI=1S/C11H15N5O3S/c1-20-2-5-7(17)8(18)11(19-5)16-4-15-6-9(12)13-3-14-10(6)16/h3-5,7-8,11,17-18H,2H2,1H3,(H2,12,13,14)/t5-,7-,8-,11-/m1/s1WUUGFSXJNOTRMR-IOSLPCCCSA-NSolidCytosollogp-0.14logs-1.66solubility6.50e+00 g/llogp-0.61pka_strongest_acidic12.47pka_strongest_basic3.92iupac(2R,3R,4S,5S)-2-(6-amino-9H-purin-9-yl)-5-[(methylsulfanyl)methyl]oxolane-3,4-diolaverage_mass297.334mono_mass297.089560061smilesCSC[C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C=NC2=C1N=CN=C2NformulaC11H15N5O3SinchiInChI=1S/C11H15N5O3S/c1-20-2-5-7(17)8(18)11(19-5)16-4-15-6-9(12)13-3-14-10(6)16/h3-5,7-8,11,17-18H,2H2,1H3,(H2,12,13,14)/t5-,7-,8-,11-/m1/s1inchikeyWUUGFSXJNOTRMR-IOSLPCCCSA-Npolar_surface_area119.31refractivity74.03polarizability29.26rotatable_bond_count3acceptor_count7donor_count3physiological_charge0formal_charge0Glutathione metabolismThe biosynthesis of glutathione starts with the introduction of L-glutamic acid through either a glutamate:sodium symporter, glutamate / aspartate : H+ symporter GltP or a
glutamate / aspartate ABC transporter. Once in the cytoplasm, L-glutamice acid reacts with L-cysteine through an ATP glutamate-cysteine ligase resulting in gamma-glutamylcysteine. This compound reacts which Glycine through an ATP driven glutathione synthetase thus catabolizing Glutathione.
This compound is metabolized through a spontaneous reaction with an oxidized glutaredoxin resulting in a reduced glutaredoxin and an oxidized glutathione. This compound is reduced by a NADPH glutathione reductase resulting in a glutathione.
PW000833ec00480MetabolicArginine and proline metabolismec00330Cysteine and methionine metabolismec00270beta-Alanine metabolismThe Beta-Alanine Metabolism starts with a product of Aspartate metabolism. Aspartate is decarboxylated by aspartate 1-decarboxylase, releasing carbon dioxide and Beta-alanine. Beta alanine is then metabolized through a pantothenate synthetase resulting in Pantothenic acid undergoes phosphorylation through a ATP driven pantothenate kinase, resulting in D-4-phosphopantothenate.
Pantothenate (vitamin B5) is the universal precursor for the synthesis of the 4'-phosphopantetheine moiety of coenzyme A and acyl carrier protein. Only plants and microorganismscan synthesize pantothenate de novo - animals require a dietary supplement. The enzymes of this pathway are therefore considered to be antimicrobial drug targets.PW000896ec00410MetabolicMetabolic pathwayseco01100Spermidine Biosynthesis ISpermidine is formed by the addition of a propylamine moiety to putrescine, catalyzed by an aminopropyltransferase termed spermidine synthase, the the product of gene speE. The source of the propylamine group is decarboxylated S-adenosyl-L-methionine (S-adenosyl-L-methioninamine) which is produced by the action of the pyruvoyl-containing enzyme adenosylmethionine decarboxylase. The other product of the aminopropyltransferase reaction is S-methyl-5'-thioadenosine (MTA), which can be recycled back to L-methionine in many organisms, but not in E. coli.
Inhibition of E. coli adenosylmethionine decarboxylase by spermidine appears to be the most significant regulator of polyamine biosynthesis, probably limiting it when the intracellular spermidine concentration becomes excessive. In E. coli most intracellular spermidine is bound to nucleic acids and phospholipids. (EcoCyc)PW002040Metabolicaminopropylcadaverine biosynthesisPolyamines are important for cell growth and are believed to be involved in many processes including DNA, RNA, and protein synthesis, as well as membrane integrity and resistance to stress, to name a few. Cadaverine and aminopropylcadaverine are alternative polyamines that can at least partially substitute for purtrescine and spermidine, the primary polyamines found in E. coli. Lysine is decarboxylated to form cadaverine which is then converted to aminopropylcadaverine by the aminopropyltransferase, SpeE. (EcoCyc)PW002039Metabolic<i>S</i>-methyl-5'-thioadenosine degradation IVPWY0-1391aminopropylcadaverine biosynthesisPWY0-1303spermidine biosynthesis IBSUBPOLYAMSYN-PWYSpecdb::CMs707Specdb::CMs9449Specdb::CMs30466Specdb::CMs31809Specdb::CMs31810Specdb::CMs37957Specdb::CMs137611Specdb::CMs145345Specdb::NmrOneD1655Specdb::NmrOneD21382Specdb::NmrOneD21383Specdb::NmrOneD21384Specdb::NmrOneD21385Specdb::NmrOneD21386Specdb::NmrOneD21387Specdb::NmrOneD21388Specdb::NmrOneD21389Specdb::NmrOneD21390Specdb::NmrOneD21391Specdb::NmrOneD21392Specdb::NmrOneD21393Specdb::NmrOneD21394Specdb::NmrOneD21395Specdb::NmrOneD21396Specdb::NmrOneD21397Specdb::NmrOneD21398Specdb::NmrOneD21399Specdb::NmrOneD21400Specdb::NmrOneD21401Specdb::MsMs1448Specdb::MsMs1449Specdb::MsMs1450Specdb::MsMs5062Specdb::MsMs5063Specdb::MsMs5064Specdb::MsMs5065Specdb::MsMs5066Specdb::MsMs5067Specdb::MsMs5068Specdb::MsMs5070Specdb::MsMs5071Specdb::MsMs178995Specdb::MsMs178996Specdb::MsMs178997Specdb::MsMs181320Specdb::MsMs181321Specdb::MsMs181322Specdb::MsMs439184Specdb::MsMs446024Specdb::MsMs446025Specdb::MsMs446026Specdb::MsMs446027Specdb::MsMs446028Specdb::MsMs447222Specdb::NmrTwoD1596HMDB01173149388321C00170175095-METHYLTHIOADENOSINEMTAKeseler, I. M., Collado-Vides, J., Santos-Zavaleta, A., Peralta-Gil, M., Gama-Castro, S., Muniz-Rascado, L., Bonavides-Martinez, C., Paley, S., Krummenacker, M., Altman, T., Kaipa, P., Spaulding, A., Pacheco, J., Latendresse, M., Fulcher, C., Sarker, M., Shearer, A. G., Mackie, A., Paulsen, I., Gunsalus, R. P., Karp, P. D. (2011). "EcoCyc: a comprehensive database of Escherichia coli biology." Nucleic Acids Res 39:D583-D590.21097882Kanehisa, M., Goto, S., Sato, Y., Furumichi, M., Tanabe, M. (2012). "KEGG for integration and interpretation of large-scale molecular data sets." Nucleic Acids Res 40:D109-D114.22080510van der Werf, M. J., Overkamp, K. M., Muilwijk, B., Coulier, L., Hankemeier, T. (2007). "Microbial metabolomics: toward a platform with full metabolome coverage." Anal Biochem 370:17-25.17765195Winder, C. L., Dunn, W. B., Schuler, S., Broadhurst, D., Jarvis, R., Stephens, G. M., Goodacre, R. (2008). "Global metabolic profiling of Escherichia coli cultures: an evaluation of methods for quenching and extraction of intracellular metabolites." Anal Chem 80:2939-2948.18331064Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4.19212411Liebich HM, Di Stefano C, Wixforth A, Schmid HR: Quantitation of urinary nucleosides by high-performance liquid chromatography. J Chromatogr A. 1997 Feb 28;763(1-2):193-7.9129323Avila MA, Garcia-Trevijano ER, Lu SC, Corrales FJ, Mato JM: Methylthioadenosine. Int J Biochem Cell Biol. 2004 Nov;36(11):2125-30.15313459Gerasimovskaya EV, Ahmad S, White CW, Jones PL, Carpenter TC, Stenmark KR: Extracellular ATP is an autocrine/paracrine regulator of hypoxia-induced adventitial fibroblast growth. Signaling through extracellular signal-regulated kinase-1/2 and the Egr-1 transcription factor. J Biol Chem. 2002 Nov 22;277(47):44638-50. Epub 2002 Sep 18.12244041Mills GC, Mills JS: Urinary excretion of methylthioadenosine in immunodeficient children. Clin Chim Acta. 1985 Mar 30;147(1):15-23.3987052Contreres JO, Dupuy E, Job B, Habib A, Bryckaert M, Rosa JP, Simoneau G, Herbert JM, Savi P, Levy-Toledano S: Effect of clopidogrel administration to healthy volunteers on platelet phosphorylation events triggered by ADP. Br J Haematol. 2003 Feb;120(4):633-42.12588350Mills GC, Schmalstieg FC, Goldblum RM: Urinary excretion of modified purines and nucleosides in immunodeficient children. Biochem Med. 1985 Aug;34(1):37-51.4052062Sufrin, Janice R.; Spiess, Arthur J.; Kramer, Debora L.; Libby, Paul R.; Porter, Carl W. Synthesis and antiproliferative effects of novel 5'-fluorinated analogs of 5'-deoxy-5'-(methylthio)adenosine. Journal of Medicinal Chemistry (1989), 32(5), 997-1001.http://hmdb.ca/system/metabolites/msds/000/001/051/original/HMDB01173.pdf?1358461858Spermidine synthaseP09158SPEE_ECOLIspeEhttp://ecmdb.ca/proteins/P09158.xml5'-methylthioadenosine/S-adenosylhomocysteine nucleosidaseP0AF12MTNN_ECOLImtnNhttp://ecmdb.ca/proteins/P0AF12.xmlS-Adenosylmethioninamine + Putrescine + Ethylenediamine <> 5'-Methylthioadenosine + Hydrogen ion + SpermidineR01920SPERMIDINESYN-RXNCadaverine + S-Adenosylmethioninamine > 5'-Methylthioadenosine + Hydrogen ion + AminopropylcadaverineR08359RXN0-52175'-Methylthioadenosine + Water > 5-Methylthioribose + AdenineR01401METHYLTHIOADENOSINE-NUCLEOSIDASE-RXN5'-Methylthioadenosine + Water <> Adenine + 5-MethylthioriboseR01401S-Adenosylmethioninamine + Putrescine <> 5'-Methylthioadenosine + SpermidineR01920SPERMIDINESYN-RXNS-Adenosylmethioninamine + Spermidine <> 5'-Methylthioadenosine + SpermineR02869S-Adenosylmethioninamine + Cadaverine <> 5'-Methylthioadenosine + AminopropylcadaverineR08359Putrescine + S-Adenosylmethioninamine > Hydrogen ion + Spermidine + 5'-MethylthioadenosineSPERMIDINESYN-RXN5'-Methylthioadenosine + Water > S-methyl-5-thio-D-ribose + AdenineS-Adenosylmethioninamine + Putrescine > 5'-Methylthioadenosine + SpermidineCadaverine + Decarboxy-SAM > Aminopropylcadaverine + 5'-Methylthioadenosine + Hydrogen ionPW_R005959Decarboxy-SAM + Putrescine > 5'-Methylthioadenosine + Spermidine + Hydrogen ionPW_R005961S-Adenosylmethioninamine + Putrescine + Ethylenediamine <>5 5'-Methylthioadenosine + Hydrogen ion + SpermidineCadaverine + S-Adenosylmethioninamine >5 5'-Methylthioadenosine + Hydrogen ion + AminopropylcadaverineS-Adenosylmethioninamine + Putrescine + Ethylenediamine <>5 5'-Methylthioadenosine + Hydrogen ion + Spermidine